Objective: To evaluate the role of insulin receptor substrate-1 (IRS-1) and glucose transporter-1 (GLUT1) gene polymorphisms in Chinese patients with noninsulin-dependent diabetes mellitus (NIDDM) and diabetic neophropathy (DN).
Methods: Aminoacid polymorphism in codon 972 of IRS-1 gene and the polymorphic Xba I site of GLUT1 gene were analyzed by PCR-RFLP in 131 patients with NIDDM and 124 normal subjects. DN was defined as persistent albuminuria and/or impaired renal function, without known cause of renal diseases other than diabetes. Insulin sensitivity index (ISI) and body mass index (BMI) were also calculated.
Results: The distribution of IRS-1 gene polymorphism showed no difference between patients with NIDDM and normal controls. The frequencies of Xba I (+/-) genotype (59% vs. 33%, P < 0.01) and Xba I (-) allele (37% vs. 21%, P < 0.01) were significantly higher in NIDDM patients than in normal subjects. To further explore the linkage of GLUT1 gene polymorphism with DN, we examined the GLUT1 genotype of NIDDM patients with or without renal damage. The frequency of Xba I (+/-) genotype (75% vs. 44%, P < 0.01) and Xba I (-) allele (44% vs. 29%, P < 0.05) was significantly higher in NIDDM patients with diabetic nephropathy than either those without nephropathy or normal subjects. However, there were no significant differences of GLUT1 genotype and allele frequency in NIDDM patients without nephropathy and normal controls. The presence of Xba I (-) allele appeared to have a strong association with the development of diabetic nephropathy. The odds ratio was 1.915, and the 95% confidence interval was 1.044-3.514. The association of Xba I (-) allele of GLUT1 gene with NIDDM partly reflected their close association with DN. Although there was no correlation between the gene polymorphism of GLUT1 and BMI, patients carrying the Xba I (-) allele showed a lower ISI.
Conclusion: No association was found between the gene polymorphism of IRS-1 and NIDDM. THe Xba I (-) allele of GLUT1 gene might be taken as a genetic marker of NIDDM with diabetic nephropathy and this genetic susceptibility appears to be associated with the insulin resistance in patients with NIDDM.